Page 9 - IBRO_RNA School_Abstract Book

Non coding RNAs as emerging players in early life adverse

experience induced violent behavior

Arpita Konar

CSIR-Institute of Genomics and Integrative Biology,

Mathura Road, Delhi, India

Violent behavior is an aberrant form of aggression that has detrimental
impact on health and society. Early life adverse experiences trigger adulthood
violence and criminality, though molecular mechanisms remain elusive. We
established peripubertal stress (PPS) induced mouse model of aggression and

investigated the molecular roots in vulnerable brain regions of prefrontal cortex
and hypothala-mus. PPS exposed male mice were violent in adulthood while
females were resil-ient to abnormal behavioral responses. Violent phenotype was
also inherited in F1 generation males who were not exposed to any
early life adversity. Transcriptome analysis revealed a significant number of brain
region specific top ranking differentially expressed long non coding RNA
(lncRNA)s in violent males and resilient females. We validated the top ranking
lncRNAs by qRT-PCR and few of them showed long lasting expression changes

from peripuberty till adulthood and even perpetuated in next generation. We
characterized these candidate lncRNAs and found them to brain enriched and
predominantly expressed in chromatin fraction. Further, we aim to determine the
molecular function of these lncRNAs and decipher whether their dynamic
expression is a cause or merely a correlate of violent behavior. Our work opens up a
new avenue of exploring lncRNAs as key predictive and/or re-covery targets of
violent aggression and other psychopathologies owing to their wide spectrum of
regulatory roles at epigenetic, transcriptional and post-transcriptional level.